In an autopsy study, 97% of individuals 50 years or older had intervertebral disc degeneration, a disease process that involves both the annulus fibrosus and nucleus pulposus [1]. The etiology of this process is unknown but may be due to the relative avascularity of the tissue [2], calcification of the cartilage endplate [3], mechanical factors [4], vertebral body microfractures [5], loss of notochordal cells and/or genetic factors [6]. The low back pain that can develop in association with this disease is one of the most common afflictions in today's society and approximately eighty percent of people will experience at least one episode of low back pain at some time in their lives [7]. The direct costs of diagnosing and treating low back pain in the United States, as estimated by the American Chiropractic Association, is approximately $25 billion annually [8]. There is no optimal treatment for chronic back pain currently. Although there are several surgical options these all have limitations. Spinal fusion of diseased disc tissue may relieve pain faster, but it can result in reduced flexibility and the potential to develop degenerative changes in adjacent segments [9]. The intervertebral disc can be replaced with a synthetic prosthesis but this treatment is only appropriate for selected individuals [10, 11] and they can loosen over time [12]. Discectomy does not restore disc height and thus does not treat the underlying disease process. Therefore, there is a great interest in developing alternative biological treatments for this disease. One of the options is to tissue engineer a functional intervertebral disc that could be used to replace the degenerated disc [13].
The human spine consists of 33 vertebral bodies each separated, with the exception of C1 and C2 and the coccyx, by an intervertebral disc (IVD). The IVD anchors adjacent vertebral bodies and by doing so allows for spinal stabilization, load bearing, and movement. The intervertebral disc is a specialized structure consisting of three components, a gel-like nucleus pulposus (NP) which is surrounded by annulus fibrosus (AF), which are sandwiched between cartilage end plates (CEP) and vertebral bodies [14]. The normal function of the disc is dependent on maintenance of the composition, organization, and integrity of the different components.
The annulus fibrosus (FIG. 3) is the most complex of these 3 tissues present in the disc. It consists of approximately 10-20 lamellar sheets each composed of collagen fibres oriented parallel to each other and about 65° C. from the vertical. Although the angle is the same, the direction of the inclination alternates with each sheet such that the fibres in one lamella are 65° to the right, while in the next lamella they are 65° to the left. Every second lamella has the same orientation. This very specific collagen organization allows the disc to rotate and flex. Collagen makes up about 70% of the dry weight of the annulus. Type I collagen is the predominant collagen but types II, III, V, VI and type IX collagen are also present in lesser amounts.
To date, many studies have focused on the regeneration of NP [15-17] rather than AF tissue, probably because of the structural complexity of the AF tissue [18]. Even though AF tissue engineering has been attempted using various polymeric scaffolds including PDLLA/45S5 Bioglass® composite films [19], atelocollagen honeycomb [20], collagen—GAG [21], collagen—hyaluronan [22], polyglycolic acid/polylactic acid [23], and alginate [24] materials, in all of these scaffolds AF tissue formation has been limited and none has recapitulated the complex structure of the AF. Furthermore some scaffolds may not be optimal for this use. For example when polylactides, polyglycolides, and their copolymers degrade, they form acidic degradation products that can decrease the local pH, and overwhelm the tissue buffering and cell regulating capacities, which adversely affect biocompatibility [25]. Furthermore an acidic environment in the disc has been shown to greatly inhibit the rates of extracellular matrix synthesis [26], which may actually affect tissue formation. For these reasons there has been an interest in developing new polymers.